Rotational acetabular osteotomy for symptomatic hip dysplasia in patients younger than 21 years of age: seven- to 30-year survival outcomes.

AIMS: The aim of this study was to report the long-term results of rotational acetabular osteotomy (RAO) for symptomatic hip dysplasia in patients aged younger than 21 years at the time of surgery. PATIENTS AND METHODS: We evaluated 31 patients (37 hips) aged younger than 21 years at the time of surgery retrospectively. There were 29 female and two male patients. Their mean age at the time of surgery was 17.4 years (12 to 21). The mean follow-up was 17.9 years (7 to 30). The RAO was combined with a varus or valgus femoral osteotomy or a greater trochanteric displacement in eight hips, as instability or congruence of the hip could not be corrected adequately using RAO alone. RESULTS: The mean Merle d'Aubigné clinical score improved significantly from 15.4 to 17.2 (p < 0.0001). The mean centre-edge (CE) angle improved from -2.6° to 26°, the mean acetabular roof angle improved from 3.0° to 5.2°, and the mean head lateralization index improved from 0.68 to 0.62. Progression of radiological osteoarthritis (OA) was seen in seven hips, but no patient underwent total hip arthroplasty. CONCLUSION: RAO is an effective form of correction for a severely dysplastic hip in adolescent and young adult patients. Cite this article: Bone Joint J 2019;101-B:390-395.

Factors affecting the potential for posterior bony impingement after total hip arthroplasty.

AIMS: Our aim was to evaluate the radiographic characteristics of patients undergoing total hip arthroplasty (THA) for the potential of posterior bony impingement using CT simulations. PATIENTS AND METHODS: Virtual CT data from 112 patients who underwent THA were analysed. There were 40 men and 72 women. Their mean age was 59.1 years (41 to 76). Associations between radiographic characteristics and posterior bony impingement and the range of external rotation of the hip were evaluated. In addition, we investigated the effects of pelvic tilt and the neck/shaft angle and femoral offset on posterior bony impingement. RESULTS: The range of external rotation and the ischiofemoral length were significantly lower, while femoral anteversion, the ischial ratio, and ischial angle were significantly higher in patients with posterior bony impingement compared with those who had implant impingement (p < 0.05). The range of external rotation positively correlated with ischiofemoral length (r = 0.49, p < 0.05), and negatively correlated with ischial length (r = -0.49, p < 0.05), ischial ratio (r =- 0.49, p < 0.05) and ischial angle (r = -0.55, p < 0.05). The range of external rotation was lower in patients with posterior pelvic tilt (p < 0.05) and in those with a high offset femoral component (p < 0.05) due to posterior bony impingement. CONCLUSION: Posterior bony impingement after THA is more likely in patients with a wider ischium and a narrow ischiofemoral space. A high femoral offset and posterior pelvic tilt are also risk factors for this type of impingement. Cite this article: Bone Joint J 2017;99-B:1140-6.

Circulating microRNAs as biomarkers for evaluating the severity of acute spinal cord injury.

STUDY DESIGN: An in vivo study in mouse models of spinal cord contusion. OBJECTIVES: To develop a novel indicator to anticipate the severity of spinal cord injury (SCI) during the acute phase and for the assessment of the efficacy of novel therapies. MicroRNAs (miRNAs) circulating in the peripheral blood are reported to modulate signaling between cells, and to be diagnostic markers for cancers. The purpose of this study was to identify circulating miRNAs for predicting the severity of SCI in the acute phase. SETTING: Department of Orthopaedic Surgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. METHODS: Mouse SCI models were made using Infinite Horizon impactor with 50 or 70 kdyn compressing power following thoracic laminectomy. The mice were then divided into four groups: normal (without surgery), sham (laminectomy only), mild (50 kdyn), and severe (70 kdyn). TaqMan low-density array analysis and real-time PCR were performed to identify candidate miRNAs that were increased in the serum relative to the severity of SCI. RESULTS: The expression levels of miR-9*, miR-219 and miR-384-5p in the serum were significantly increased relative to the severity of SCI 12 h after injury. The expression of miR-9* was also significantly increased relative to injury severity at 3 and 24 h after injury. CONCLUSION: Serum miR-9*, miR-219 and miR-384-5p might be promising biomarkers for predicting the severity of SCI.

Are cam and pincer deformities as common as dysplasia in Japanese patients with hip pain?

In Japan, osteoarthritis (OA) of the hip secondary to acetabular dysplasia is very common, and there are few data concerning the pathogeneses and incidence of femoroacetabular impingement (FAI). We have attempted to clarify the radiological prevalence of painful FAI in a cohort of Japanese patients and to investigate the radiological findings. We identified 176 symptomatic patients (202 hips) with Tönnis grade 0 or 1 osteoarthritis, whom we prospectively studied between August 2011 and July 2012. There were 61 men (65 hips) and 115 women (137 hips) with a mean age of 51.8 years (11 to 83). Radiological analyses included the α-angle, centre-edge angle, cross-over sign, pistol grip deformity and femoral head neck ratio. Of the 202 hips, 79 (39.1%) had acetabular dysplasia, while 80 hips (39.6%) had no known aetiology. We found evidence of FAI in 60 hips (29.7%). Radiological FAI findings associated with cam deformity were the most common. There was a significant relationship between the pistol grip deformity and both the α-angle (p < 0.001) and femoral head-neck ratio (p = 0.024). Radiological evidence of symptomatic FAI was not uncommon in these Japanese patients.

Sugar expression in the mucosae of the canine uterus and vagina during the oestrous cycle and with pyometra.

The pathogenesis of canine pyometra is still unclear, but bacterial infection of the endometrium, mediated by bacterial lectins, is suspected to induce pyometra. The aim of this study was to investigate sugar expression in the mucosae of the uterus and vagina of healthy dogs with normal oestrous cycles and in dogs with pyometra, using a panel of lectins to investigate the pathogenesis of pyometra. In dogs with pyometra, the uterine and vaginal mucosae were positive for lectins that selectively bind to glucose or mannose, especially during days 7-10 and 30-40 of dioestrus. These results suggest that temporal changes in sugar expression in the uterus and vagina present an opportunity for pathogens to infect the endometrium, causing pyometra.

Enhancement of bone formation in an experimental bony defect using ferumoxide-labelled mesenchymal stromal cells and a magnetic targeting system.

We used interconnected porous calcium hydroxyapatite ceramic to bridge a rabbit ulnar defect. Two weeks after inducing the defect we percutaneously injected rabbit bone marrow-derived mesenchymal stromal cells labelled with ferumoxide. The contribution of an external magnetic targeting system to attract these cells into the ceramic and their effect on subsequent bone formation were evaluated. This technique significantly facilitated the infiltration of ferumoxide-labelled cells into ceramic and significantly contributed to the enhancement of bone formation even in the chronic phase. As such, it is potentially of clinical use to treat fractures, bone defects, delayed union and nonunion.

Bone-marrow-derived mononuclear cells with a porous hydroxyapatite scaffold for the treatment of osteonecrosis of the femoral head: a preliminary study.

We have investigated the effectiveness of the transplantation of bone-marrow-derived mononuclear cells (BMMNCs) with interconnected porous calcium hydroxyapatite (IP-CHA) on early bone repair for osteonecrosis of the femoral head. We studied 22 patients (30 hips) who had osteonecrosis with a minimum follow-up of one year after implantation of BMMNCs. The mean age at surgery was 41 years (18 to 64) and the mean period of follow-up was 29 months (19 to 48). In a control group, cell-free IP-CHA was implanted into a further eight patients (9 hips) with osteonecrosis of the femoral head and the outcomes were compared. A reduction in the size of the osteonecrotic lesion was observed subsequent to hypertrophy of the bone in the transition zone in the BMMNC group. In three patients in the treatment group progression to extensive collapse was detected. In the control group subtle bone hypertrophy was observed, but severe collapse of the femoral head occurred in six of eight hips. In this limited study the implantation of BMMNCs and IP-CHA appears to confer benefit in the repair of osteonecrosis and in the prevention of collapse.

Histological and biomechanical study of impacted cancellous allografts with cement in the femur: a canine model.

INTRODUCTION: An experimental canine model was used for quantitative histological study using bone morphometry and biomechanical study on impacted cancellous allografting with cement in revision total hip arthroplasty. MATERIALS AND METHODS: The prosthesis had a collarless polished titanium alloy tapered stem with a head diameter of 15 mm. Twelve Beagle dogs were used. Cancellous bone grafts were obtained aseptically from the femoral condyles of other beagles. Histological examinations were performed up to 1 year after surgery. Biomechanical examinations were performed at 8 weeks after surgery. RESULTS: The new bone formation proceeded from the proximal part to the distal site of the femur in the long axis as well as from the host cortical bone to the cement layer. Bone morphometry showed that the mineral apposition rate was higher in the proximal site of the femur than in the distal site at 8 weeks after surgery, but no significant differences were observed at other times. The bone formation rate was higher in the proximal site of the femur at 8 weeks after surgery, while it increased in the distal site at 16 weeks postoperatively but had decreased at 1 year after surgery significantly. The load test at 8 weeks after surgery showed that there was no significant difference at all sites attached strain gauge between impacted cancellous allograft group and control group. CONCLUSION: We concluded that biological replacement of the grafted bone by new bone settled at 1 year after surgery in this experimental model. However, the process was not completed.

Possibility of selection of chondrogenic progenitor cells by telomere length in FGF-2-expanded mesenchymal stromal cells.

Telomere length plays an important role in regulating the proliferative capacity of cells, and serves as a marker for cell cycle history and also for their remaining replicative potential. Mesenchymal stromal cells (MSC) are known to be a significant cell source for therapeutic intervention and tissue engineering. To investigate any possible limitations in the replicative potential and chondrogenic differentiation potential of fibroblast growth factor-2-expanded MSCs (FGF(+)MSC), these cells were differentiated at various population doublings (PDs), and telomere length and telomerase activity were measured before and after differentiation. FGF(+)MSC cultured at a relatively low density maintained proliferation capability past more than 80 PD and maintained chondrogenic differentiation potential up to at least 46 PD and long telomeres up to 105 PD, despite expressing low levels of telomerase activity. Interestingly, upon chondrogenic differentiation of these cells, telomeres showed a remarkable reduction in length. This shortening was more extensive when FGF(+)MSC of higher PD levels were differentiated. These findings suggest that telomere length may be a useful genetic marker for chondrogenic progenitor cells.

A histological study of articular cartilage after rotational acetabular osteotomy for hip dysplasia.

Acetabular dysplasia was produced in 24 immature white rabbits. A rotational acetabular osteotomy was then carried out and radiological and histological studies of the articular cartilage were made. In the hips which did not undergo osteotomy, radiographs at 26 weeks showed that residual subluxation remained and arthritic changes such as narrowing of the joint space or dislocation were still seen. However, in the operated group there was a remarkable increase in cover, but arthritic changes were not observed. After 24 weeks, the Mankin grading score in the operated group was significantly lower than that in the non-operated group. The latter hips showed an irregular surface of the cartilage, exfoliation and proliferation of synovial tissue. In those undergoing osteotomy, primary cloning of chondrocytes or hypercellularity was seen and at 24 weeks after operation and metaplasia of the cartilage in the fibrous tissue was observed in the boundary between the medial area of the acetabulum and the acetabular fossa.

Curved varus femoral osteotomy for minimal dysplastic hip in patients older than 45 years of age: comparison with rotational acetabular osteotomy.

Periacetabular osteotomies, such as rotational acetabular osteotomy (RAO) for osteoarthritis (OA) secondary to hip dysplasia, have produced satisfactory medium- and long-term results in early OA. However, as the degree of surgical invasion of these procedures is comparatively major and long-term postoperative rehabilitation is required, this procedure is generally not indicated for those in the fifth and sixth decades of life. Curved varus femoral osteotomy (CVO), which is a less invasive procedure, is considered a worthwhile option, although to the best of our knowledge no comparative study has been reported on these two procedures in older patients. We performed a comparative study on the outcomes of CVO for minimal dysplasia of the hip with a center-edge (CE) angle greater than 5 degrees in 15 patients (15 joints) older than 45 years of age at a mean period of 8 years after surgery and on the outcomes of RAO in 16 patients (18 joints) performed during the same period. No significant difference was observed between the two groups regarding the Merle d'Aubigne score during follow-up. Progression of osteoarthritis was radiologically observed during follow-up in three hips in the CVO group and in one hip in the RAO group. Kaplan-Meier survivorship analysis, with radiological progression of osteoarthritis as the endpoint, predicted a survival rate of 75% at 10 years in the CVO group. In the RAO group the predicted 10-year survival rate was 94%, demonstrating no significant difference between the two groups. CVO is a less invasive surgical technique than RAO, requires a comparatively shorter period of postoperative rehabilitation, and is useful as a joint-preserving procedure in older patients with minimal dysplasia of the hip with unilateral involvement. CVO should be selected for elderly patients with a CE angle greater than 5 degrees .

Rotational acetabular osteotomy in patients forty-six years of age or older: comparison with younger patients.

BACKGROUND: Satisfactory intermediate and long-term results of periacetabular rotational osteotomy for early osteoarthritis secondary to dysplasia of the hip have been reported for patients in the third and fourth decades of life. The purpose of the present study was to examine the usefulness of rotational acetabular osteotomy in patients older than forty-six years of age. METHODS: A retrospective review of two groups of patients who had been treated with a rotational acetabular osteotomy was conducted. The older group consisted of twenty-four patients (twenty-six hips) with early-stage osteoarthritis who had a mean age at the time of surgery of 50.9 years (range, forty-six to fifty-eight years) and a mean duration of follow-up of 8.2 years (range, five to thirteen years), and the younger group consisted of sixty patients (sixty-three hips) who had a mean age at the time of surgery of 34.4 years (range, thirteen to forty-five years) and a mean duration of follow-up of 8.3 years (range, five to fourteen years). Clinical follow-up was based on the system of Merle d'Aubigne and Postel. The center-edge angle, acetabular roof angle, and head lateralization index were measured on radiographs made preoperatively, postoperatively, and at the time of follow-up. Preoperative and postoperative joint congruencies were classified into four grades. RESULTS: Preoperatively, the mean Merle d'Aubigne clinical score was 13.9 points in the older group and 14.1 points in the younger group. In both groups, this score improved significantly to a mean postoperative follow-up score of 16.6 points (p < 0.0001), with no significant difference between the two groups. The mean center-edge angle improved from 3.2 degrees preoperatively to 34 degrees postoperatively (p < 0.0001) in the older group and from -2.1 degrees preoperatively to 34 degrees postoperatively (p < 0.0001) in the younger group. The mean acetabular roof angle improved from 29 degrees to 5.9 degrees (p < 0.0001) in the older group and from 31 degrees to 2.9 degrees (p < 0.0001) in the younger group. The mean head lateralization index improved from 0.67 to 0.64 (p < 0.01) in the older group and from 0.66 to 0.61 (p < 0.0001) in the younger group. Progression of osteoarthritis was observed radiographically at the time of follow-up in five hips in the older group and in four hips in the younger group. Kaplan-Meier survivorship analysis, with radiographic progression of osteoarthritis as the end point, predicted a ten-year survival rate of 70.0% in the older group and 93.7% in the younger group; this difference was not significant, with the numbers available (p = 0.062, log-rank test). CONCLUSIONS: Our results indicate that rotational acetabular osteotomy for elderly patients can prevent progression of osteoarthritis (as indicated by a survival rate of 70% at ten years) and that in selected cases it is worthwhile at least as a temporizing operation.

A novel human cancer culture model for the study of prostate cancer.

Research into molecular and genetic mechanisms underlying prostate carcinogenesis would be greatly advanced by in vitro models of prostate tumors representing primary tumors. We have successfully established an immortalized human prostate epithelial (HPE) cell culture derived from a primary tumor with telomerase. The actively proliferating early passaged RC-58T cells were transduced through infection with a retrovirus vector expressing the human telomerase catalytic subunit (hTERT). A high level of telomerase was detected in RC-58T/hTERT cells but not RC-58T cells. RC-58T/hTERT cells are currently growing well at passage 50, whereas RC-58T cells senesced at passage 7. RC-58T/hTERT cells exhibit transformed morphology. More importantly, these immortalized cells showed anchorage-independent growth as they formed colonies in soft agar and grew above the agar layer. Expression of androgen-regulated prostate specific gene NKX3.1 and epithelial specific cytokeratin 8 (CK8) but not prostate specific antigen (PSA) and androgen receptor was detected in RC-58T/hTERT cells. Prostate stem cell antigen (PSCA) and p16 were also expressed in this cell line. RC-58T/hTERT cells showed growth inhibition when exposed to retinoic acid and transforming growth factor (TGF)-beta1 known potent inhibitors of prostate epithelial cell growth. A number of chromosome alterations were observed including the loss of chromosomes Y, 3p, 10p, 17p, 18q and the gain of chromosomes 16 and 20. These results demonstrate that this primary tumor-derived HPE cell line retained its transformed phenotypes and should allow studies to elucidate molecular and genetic alterations involved in prostate cancer. This is the first documented case of an established human prostate cancer cell line from a primary tumor of a prostate cancer patient with telomerase.

The state of the articular cartilage at the time of surgery as an indication for rotational acetabular osteotomy.

We have studied whether the state of the articular cartilage at the time of rotational acetabular osteotomy for dysplasia of the hip affects the outcome 2 to 5.5 years after surgery. Arthroscopy in 57 patients (59 joints) at the time of the operation showed grade-0 changes in seven, grade-1 in nine, grade-2 in 17, grade-3 in 14 and grade-4 in 12 joints, according to the classification of Outerbridge. There was radiological evidence of the progression of arthritis in four joints which were classified at arthroscopy as grade 4. Stepwise regression analysis showed that damage to acetabular or femoral articular cartilage significantly affected the progression of arthritis. We conclude that the short-term results of successful rotational acetabular osteotomy for dysplasia are affected by the state of the articular cartilage.

A novel human cell culture model for the study of familial prostate cancer.

Research into molecular and genetic mechanisms underlying familial prostate cancer would be greatly advanced by in vitro models of prostate tumor cells representing primary tumors. We have successfully established an immortalized human prostate epithelial cell culture derived from primary tumors of familial prostate cancer patients with telomerase. The actively proliferating early-passaged 957E cells were transduced through infection with a retrovirus expressing the human telomerase catalytic subunit, human telomerase reverse transcriptase (hTERT). A high level of telomerase activity was detected in 957E/hTERT cells, but not in 957E cells. 957E/hTERT cells are currently growing well at passage 40, whereas 957E cells senesced at passage 5. 957E/hTERT cells exhibit epithelial morphology. Expression of an androgen-regulated prostate specific homeobox gene NKX3.1 and an epithelial cell-specific cytokeratin 8, but not prostate specific antigen or androgen receptor, was detected in 957E/hTERT cells. Prostatic stem cell antigen and p16 were also expressed in this line. 957E/hTERT cells showed growth inhibition when exposed to retinoic acid and transforming growth factor beta1, potent inhibitors of prostate epithelial cell growth. Chromosome analysis showed that the 957E/hTERT cell line (passage 10) was near diploid human male (XY), with most chromosome counts in the 44-46 range. However, there was random loss of chromosomes 8, 13, X, Y, and alteration in chromosome 4q. The late passage 957E/hTERT cell line (passage 32) was karyologically similar to the early passage 957E/hTERT cell line (passage 10) and also had the same alteration of 4q observed in the early passage 957E/hTERT cell line (passage 10) as well as a trisomy of chromosome 20. The well-characterized human cancer lines derived from such patients will be useful for the identification and characterization of prostate cancer susceptibility genes. This is the first documented case of an established human prostate cancer cell line from primary tumor of a familial prostate cancer patient.

Retrovesical desmoplastic small round cell tumor in a patient with urinary frequency.

A 21-year-old man with urological symptoms was found to have a large abdominal tumor in the retrovesical space between the bladder and the rectosigmoid colon. Radiologic findings revealed little evidence confirming the diagnosis. A transrectal biopsy failed to disclose the histopathologic origin of the tumor. An exploratory laparotomy with a complete surgical resection was impossible, so a wedge biopsy was performed. Combined histologic and immunohistochemical findings revealed the features of desmoplastic small round cell tumor (DSRCT). Despite subsequent multi-agent chemotherapy, the patient died as a result of the growing tumor and liver metastasis. There have been only two prior reports of this neoplasm in the urological literature.

Rotational acetabular osteotomy for hip dysplasia: spontaneous medial enlargement of the acetabulum.

We followed 56 patients (63 joints) who had undergone rotational acetabular osteotomy (RAOs) between 1987 and 1993, mean 7 (5-12) years. The Merle d'Aubigné score increased by 15 points or more in 59 and decreased in 4 hips. The arthrosis progressed in 5 joints. In about 2/3 of the cases, we observed some medial and/or lateral expansion of the subchondral bone in the acetabulum 3 years postoperatively, suggesting enlargement of the load-bearing area.

A histological study of the necrotic area after transtrochanteric anterior rotational osteotomy for osteonecrosis of the femoral head.

We studied nine patients who had had a transtrochanteric anterior rotational osteotomy, as developed by Sugioka, for osteonecrosis of the femoral head. At a mean of 2.5 years after the initial operation we carried out a histological study of the previously necrotic femoral head which had not shown collapse of the new primary weight-bearing site. In seven joints, there was proliferation of fibrous tissue in the dead trabeculae with vascular ingrowth. New bone covering dead trabeculae created the characteristic appearance of 'creeping substitution'. However, these changes were limited and did not extend over the entire necrotic area. Dead bone remained in all the cases. In the other two heads we did not observe proliferation of fibrous tissue or vascular ingrowth, only dead trabeculae and dead bone marrow.

Repair of articular cartilage on the surface of heat-treated bone by transplantation of cultured chondrocytes.

The present study addresses clinical problems associated with the degeneration of articular cartilage, which occurs when heat-treated bone with articular cartilage is used for re-implantation after resection of malignant bone tumors adjacent to the joints. We therefore evaluated the effect of transplantation of chondrocytes embedded in collagen gel on the surface of heat-treated bone. A cylindrical complex of bone and articular cartilage 6 mm in diameter was resected from rabbits' patellar grooves and treated in saline at 60 degrees C for 30 min. In Group A, articular cartilage was resected from the complex and the remaining bone was returned to the patellar groove. Then, autologous chondrocytes cultured in collagen gel were transplanted and covered with periosteum. As controls, the original complex of heat-treated bone and articular cartilage (Group B) and heat-treated bone directly covered with periosteum (Group C) was returned to the patellar groove. In Group A, histological study showed that round cells were mainly observed and the matrix was well stained with Safranin O in the repair tissue after 24 weeks. The repair tissue was as thick as the adjacent normal cartilage. Immunohistological study detected type-II collagen and chondroitin-6-sulphate (3B3+) in the matrix of the repair tissue, but not type-I collagen. The repair tissue was consequently cartilaginous in Group A. The repair tissue was not cartilaginous or was degenerative in the control groups. We believe that this modality of heat-treated joints will contribute to limb salvage reconstruction after resection of malignant bone tumors adjacent to the joints.